title: Psychosis in Alzheimer's disease.
abstract: Psychotic symptoms, delusions and hallucinations, occur in approximately 50% of individuals with Alzheimer's disease (AD) (AD with psychosis [AD + P]). Pharmacotherapies for AD + P have limited efficacy and can increase short-term mortality. These observations have motivated efforts to identify the underlying biology of AD + P. Psychosis in AD indicates a more severe phenotype, with more rapid cognitive decline beginning even before psychosis onset. Neuroimaging studies suggest that AD + P subjects demonstrate greater cortical synaptic impairments than AD subjects without psychosis, reflected in reduced gray matter volume, reduced regional blood flow, and reduced regional glucose metabolism. Neuroimaging and available postmortem evidence further indicate that the impairments in AD + P, relative to AD subjects without psychosis, are localized to neocortex rather than medial temporal lobe. Neuropathologic studies provide consistent evidence of accelerated accumulation of hyperphosphorylated microtubule associated protein tau in AD + P. Finally, studies of familial aggregation of AD + P have established that the risk for psychosis in AD is, in part, genetically mediated. Although no genes are established as associated with AD + P, the first genome-wide association study of AD + P has generated some promising leads. The study of the neurobiology of AD + P is rapidly accelerating and may be poised for translational discovery. This process can be enhanced by identifying points of convergence and divergence with the neurobiology of AD proper and of schizophrenia, by innovative extension of current approaches, and by development of relevant animal models.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania; Veterans Integrated Service Network 4 Mental Illness Research, Education and Clinical Center, US Department of Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Murray
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Mary Ann A
authors.initials: MA
authors.lastname: Demichele-Sweet
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania; Veterans Integrated Service Network 4 Mental Illness Research, Education and Clinical Center, US Department of Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania. Electronic address: sweetra@upmc.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology; D003071:Cognition; D005260:Female; D006801:Humans; D008297:Male; D011618:Psychotic Disorders / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*
keywords: Alzheimer’s disease; genetics; heritability; neuroimaging; neuropathology; psychosis